The proposed study aims at understanding the mechanism of action of cocaine by determination of the metabolism, both acute and chronic, of the compound and its interaction with other drugs. C14-cocaine labeled on the N-methyl group and nonlabeled norcocaine were prepared for metabolic studies. In rats receiving C14-cocaine (40 milligram/kg, s.c.) a total of 10% demethylation, in the form of C14O2, was detected in 8 hr. Following an i.v. administration, 60 and 30% of radioactivity were excreted in rat urine and feces, respectively, in 24-hr, and nearly all the radioactivity was recovered at 48 hr. The effect of varying i.p. doses of cocaine, norcocaine benzoylecognine, and tropacocaine on locomotor activity of rats has been studied. A "stimulation state" appeared in animals, as measured by the motor activity, after continuous injections of cocaine for seven days. Cocaine (20 milligrams/kg, i.p.) caused diminution of rat brain serotonin but had no effect on norepinephrine and dopamine. A 50% decrease in normetanephrine was observed 15 min. after injection of cocaine, while no detectable change of 5-hydroxyindoleacetic acid was evident.